BACKGROUND: The study aimed to evaluate the impact of integrating molecular classification with imaging-based preoperative staging on risk stratification prediction in endometrial cancer patients in accordance with ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) 2021 guidelines. METHODS: A retrospective cohort of 143 endometrial cancer patients was analyzed to assess changes in preoperative risk stratification after incorporating molecular classification into clinical evaluation. Preoperative clinical staging was primarily based on transvaginal ultrasound imaging. The overall agreement between preoperative risk group estimates (with/without molecular classification) and final postoperative outcomes was assessed using weighted Cohen's Kappa, with bootstrap 95% confidence intervals and quadratic weights. RESULTS: The addition of molecular classification significantly improved preoperative risk stratification accuracy (from 59.4 to 73.4%), particularly for patients post-operatively classified as high-risk. Kappa values indicated an improvement in overall agreement between preoperative and postoperative risk stratification following the addition of molecular classification, from 0.551 (95% CI: 0.430-0.671) to 0.767 (95% CI: 0.675-0.849). The non-overlapping confidence intervals indicated statistical significance. Preoperative assessment without molecular input tended to underestimate risk stratification. However, 26.6% of patients remained misclassified due to other factors, mostly within the intermediate and high-intermediate risk groups. CONCLUSIONS: Incorporating molecular classification enhances preoperative risk stratification and has the potential to tailor surgical treatment. Further validation through prospective multicentric studies is needed to support our findings.

• Klíčová slova
• ESGO/ESTRO/ESP 2021 guidelines, Endometrial cancer, Molecular classification, Next-generation sequencing, Risk stratification, Sentinel node biopsy, Ultrasonography,
• MeSH
• dospělí MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory endometria * chirurgie   patologie   klasifikace   diagnostické zobrazování   genetika   diagnóza   MeSH
• předoperační období MeSH
• předoperační péče MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Molecular classification of endometrial carcinomas (EC) divides these neoplasms into four distinct subgroups based on their molecular background. Given its clinical significance, genetic examination is becoming integral to the diagnostic process. This study aims to share our experience with the molecular classification of EC using immunohistochemistry (IHC) and next-generation sequencing (NGS). We included all ECs diagnosed at two institutions from 2020 to the present. All cases were prospectively examined by IHC for MMR proteins and p53, followed by NGS using a customized panel covering 18 genes, based on which ECs were classified into four molecular subgroups: POLE mutated, hypermutated (MMR deficient), no specific molecular profile (NSMP), and TP53 mutated. The cohort comprised 270 molecularly classified ECs: 18 (6.6%) POLE mutated, 85 (31.5%) hypermutated, 137 (50.7%) NSMP, and 30 (11.1%) TP53 mutated. Twelve cases (4.4%) were classified as 'multiple classifier' EC. Notably, most of these cases with available follow-up (6/9) behaved aggressively. Within the POLEmut EC group, 3/4 cases had advanced tumors, including one patient who died of the disease. Similarly, in the MMRd/TP53mut group, 3/5 patients with available follow-up had metastatic disease, leading to death of the patient in 1 case. ECs of NSMP showed multiple genetic alterations, with the most common mutations being PTEN (44% within the group of NSMP), followed by PIK3CA (30%), ARID1A (21%), and KRAS (9%). Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.

• Klíčová slova
• Endometrial carcinoma, Molecular classification, Multiple classifier, Next-generation sequencing,
• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory endometria * genetika   patologie   klasifikace   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery * MeSH
• nádorový supresorový protein p53 MeSH
• TP53 protein, human MeSH Prohlížeč

BACKGROUND: While sentinel lymph node (SLN) biopsy has been integrated into international guidelines for endometrial cancer, a standardized technique is still lacking. This study addresses whether the concurrent use of two tracers, technetium-99 (Tc) and indocyanine green (ICG), administered intracervically through distinct techniques, enhances the performance of SLN biopsies. As the blue dye is used routinely by some centers, it can be used alone; however, our analysis focused on only Tc and ICG (as is used in the majority of centers). METHODS: A prospective multicentric observational study was designed to evaluate the unilateral detection rate, bilateral detection rates, sensitivity, and consistency of SLNs when using both tracers simultaneously in patients with early-stage endometrial cancer. RESULTS: Our findings demonstrated that the simultaneous use of ICG and Tc significantly outperformed the use of either tracer alone. Unilateral detection rates were 69.2% for Tc, 84.9% for ICG, and 88.4% for both. Bilateral detection rates were 57.0% for Tc, 77.9% for ICG, and 83.6% for both. Additionally, the incidence of "empty pockets" was low with both tracers, at 2.7%. Notably, the concurrent application of both tracers identified instances where the Tc-labeled sentinel node differed from the ICG-labeled sentinel node. CONCLUSIONS: The combined use of Tc and ICG in SLN biopsy for early-stage endometrial cancer significantly enhances detection rates and reduces the occurrence of "empty pockets", potentially decreasing the need for site-specific lymphadenectomy.

• Klíčová slova
• endometrial cancer, sentinel lymph node, tracer,
• Publikační typ
• časopisecké články MeSH

Minimally invasive surgery is the method of choice in endometrial cancer. Experience in procedures assisted by a robotic system is growing rapidly. One of the new bipolar ones is a Vessel Sealer, with sealing and cutting function. The aim of the study was to compare robotic surgery assisted with the da Vinci X system with use of the Vessel Sealer or without it. The study included 25 patients with high-risk endometrial cancer after completed pelvic and paraaortic lymphadenectomy with mean age 60.07 ± 10.67 (range 34.69-83.23) years divided into two groups: one with use of the Vessel Sealer; the second one only with monopolar scissors and subdivided by one-site versus dual docking. Duration of the operation was significantly associated with previous surgery (p < 0.005). Use of the Vessel Sealer was associated with lower blood loss during surgery (p < 0.05). The number of removal pelvic lymph nodes was higher in case of Vessel Sealer with no relation to BMI. Experience in robotic surgery allowed for shortened operation time and led to better outcomes. The Vessel Sealer used in robotic surgery appears to reduce blood loss during surgery and operation time, especially in the case of previous surgery, however, it increases costs of the procedure.

• Klíčová slova
• Bipolar device, Endometrial cancer, Paraaortic lymphadenectomy, Robotic surgery,
• MeSH
• délka operace MeSH
• dospělí MeSH
• krvácení při operaci prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie * metody   přístrojové vybavení   MeSH
• nádory endometria * chirurgie   patologie   MeSH
• roboticky asistované výkony * metody   přístrojové vybavení   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

(1) The surgical method of choice for the treatment of endometrial cancer is minimally invasive surgery. In cases of high-risk endometrial cancer, completed paraaortic and pelvic lymphadenectomy are indicated. The aim of this study was to analyze the types of docking during robotic surgery assisted with the da Vinci X system while performing paraaortic and pelvic lymphadenectomy. (2) Methods: A total of 25 patients with high-risk endometrial cancer, with a mean age of 60.07 ± 10.67 (range 34.69-83.23) years, and with a mean body mass index (BMI) of 28.4 ± 5.62 (range 18-41.5) kg/m2, were included in this study. The analyzed population was divided into groups that underwent single or dual docking during surgery. (3) Results: No statistical significance was observed between single and dual docking during paraaortic and pelvic lymphadenectomy and between the type of docking and the duration of the operation. However, there was a statistically significant correlation between the duration of the operation and previous surgery (p < 0.005). The number of removed lymph nodes was statistically associated with BMI (p < 0.005): 15.87 ± 6.83 and 24.5 ± 8.7 for paraaortic and pelvic lymph nodes, respectively, in cases of single docking, and 18.05 ± 7.92 and 24.88 ± 11.75 for paraaortic and pelvic lymph nodes, respectively, in cases of dual docking. (4) Conclusions: The robot-assisted approach is a good surgical method for lymphadenectomy for obese patients, and, despite the type of docking, there are no differences in the quality of surgery.

• Klíčová slova
• dual docking, endometrial cancer, paraaortic lymphadenectomy, robotic surgery, single docking,
• Publikační typ
• časopisecké články MeSH

In recent years the role of diagnostic imaging by pelvic ultrasound in the diagnosis and staging of gynecological cancers has been growing exponentially. Evidence from recent prospective multicenter studies has demonstrated high accuracy for pre-operative locoregional ultrasound staging in gynecological cancers. Therefore, in many leading gynecologic oncology units, ultrasound is implemented next to pelvic MRI as the first-line imaging modality for gynecological cancer. The work herein is a consensus statement on the role of pre-operative imaging by ultrasound and other imaging modalities in gynecological cancer, following European Society guidelines.

• Klíčová slova
• cervical cancer, cross-sectional studies, ovarian cancer, uterine cancer, vulvar and vaginal cancer,
• MeSH
• gynekologie * MeSH
• konsensus MeSH
• lidé MeSH
• nádory ženských pohlavních orgánů * diagnostické zobrazování   MeSH
• pánev MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific-(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC.

• Klíčová slova
• CA125, advanced stage, endometrial cancer, high-grade, outcome,
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. OBJECTIVE: To determine the association of molecular profiling with outcomes among patients with low-grade EC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. EXPOSURES: Molecular testing of the 4 molecular subgroups. MAIN OUTCOMES AND MEASURES: The main outcome was disease-specific survival (DSS) within the molecular subgroups. RESULTS: A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS. CONCLUSIONS AND RELEVANCE: This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness.

• MeSH
• endometroidní karcinom * patologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory endometria * MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

INTRODUCTION: Among industrialized countries, endometrial cancer is a common malignancy with generally an excellent outcome. To personalize medicine, we ideally compile as much information as possible concerning patient prognosis prior to effecting an appropriate treatment decision. Endometrial cancer preoperative risk stratification (ENDORISK) is a machine learning-based computational Bayesian networks model that predicts lymph node metastasis and 5-year disease-specific survival potential with percentual probability. Our objective included validating ENDORISK effectiveness in our patient cohort, assessing its application in the current use of sentinel node biopsy, and verifying its accuracy in advanced stages. METHODS: The ENDORISK model was evaluated with a retrospective cohort of 425 patients from the University Hospital Brno, Czech Republic. Two hundred ninety-nine patients were involved in our disease-specific survival analysis; 226 cases with known lymph node status were available for lymph node metastasis analysis. Patients were included undergoing either pelvic lymph node dissection (N = 84) or sentinel node biopsy (N =70) to explore the accuracy of both staging procedures. RESULTS: The area under the curve was 0.84 (95% confidence interval [CI], 0.77-0.9) for lymph node metastasis analysis and 0.86 (95% CI, 0.79-0.93) for 5-year disease-specific survival evaluation, indicating quite positive concordance between prediction and reality. Calibration plots to visualize results demonstrated an outstanding predictive value for low-risk cancers (grades 1-2), whereas outcomes were underestimated among high-risk patients (grade 3), especially in disease-specific survival. This phenomenon was even more obvious when patients were subclassified according to FIGO clinical stages. CONCLUSIONS: Our data confirmed ENDORISK model's laudable predictive ability, particularly among patients with a low risk of lymph node metastasis and expected favorable survival. For high-risk and/or advanced stages, the ENDORISK network needs to be additionally trained/improved.

• Klíčová slova
• Bayesian networks model, disease-specific survival, endometrial cancer, lymph node metastasis, prognosis, risk stratification, sentinel node biopsy,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Endometrial cancer is the most common gynecological malignancy in developed countries with no screening available. There is still a tendency to provide invasive bioptic verification in asymptomatic women with abnormal ultrasound findings to diagnose carcinoma in a preclinical phase; even though, it is not supported by European guidelines. Our goal was to determine DFS (disease-free survival), OS (overall survival), and DSS (disease-specific survival) differences between symptom-free and symptomatic (bleeding, or spotting) endometrial cancer patients with similar stage and tumor/clinical characteristics. METHODS: All of our patients with endometrial cancer following surgical treatment between 2006 and 2019 were assessed, evaluating risk factors for recurrence and death while focusing on bleeding using univariable and multivariable analysis. RESULTS: 625 patients meeting the inclusion criteria were divided into asymptomatic (n = 144, 23%) and symptomatic (n = 481, 77%) groups. The median follow-up was 3.6 years. Using univariable analysis, symptomatic patients had a three times higher risk of recurrence (HR 3.1 (95% Cl 1.24-7.77), p = 0.016). OS (HR 1.35 (0.84-2.19), p = 0.219) and DSS (HR 1.66 (0.64-4.28), p = 0.3) were slightly worse without reaching statistical significance. In our multivariable analysis, symptomatology was deemed completely insignificant in all monitored parameters (DFS: HR 2.03 (0.79-5.24), p = 0.144; OS: HR 0.72 (0.43-1.21), p = 0.216). CONCLUSIONS: The symptomatic endometrial cancer patients risk factor of earlier recurrence and death is insignificantly higher when compared with the asymptomatic cohort. However, multivariable analysis verifies that prognosis worsens with other clinically relevant parameters, not by symptomatology itself. In terms of survival outcome in EC patients, we recognized symptomatology as a non-significant marker for the patient's prognosis.

• Klíčová slova
• endometrial cancer, postmenopausal bleeding, prognosis,
• Publikační typ
• časopisecké články MeSH